In recent years, sodium-glucose cotransporter-2 inhibitors (SGLT2i) and others have been approved as new candidates for oral hypoglycemic agents (OHAs), which are expected to provide various benefits. There are, however, still some uncertainties about adverse drug reactions. This study investigated the association between OHA and liver injury (LI) from various angles using the Japanese Adverse Drug Event Report (JADER) database. Total 668 cases for around past 16 years were found from the database and the results of the analysis using the Evaluation index of Risk for incident LI (EiRiLI) developed by the authors indicated that the risk of adverse reactions in dipeptidyl peptidase-4 inhibitors (DPP-4i) and SGLT2i could be two to five times higher than that of other medications. According to the case reports reviewed in this study, LI was the most common adverse reaction. The diagnosis was based mostly on drug-induced lymphocyte stimulation test (DLST) and it was indicated that the allergic mechanisms could account for more than half of all cases. Concerning the period between the administration of drugs and the development of LI (latent period), these medicines appeared to have a higher incidence of LI with longer medication use than other drugs. Further study is required for the risk of DPP-4i and SGLT2i-induced LI, which is considered high according to the EiRiLI. Moreover, if immunological mechanism is considered to be involved in adverse reactions to the drugs, mid- to long-term monitoring from the start of administration is required to take their characteristic latent period into account.